Title ELECTRONARCOSIS by DIRECT STIMULATION OF

ELECTRONARCOSIS BY DIRECT STIMULATION OF Title THE BRAIN STEM

Author(s) ASAI, SHIGEZO

Citation 日本外科宝函 (1958), 27(1): 21-40

Issue Date 1958-01-01

URL http://hdl.handle.net/2433/206591

Right

Type Departmental Bulletin Paper

Textversion publisher

Kyoto University 21 21

原著

ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM

by SHIGEZO SHIGEZO ASAI From the lrst Surgical Division, Kyoto University Medical school (Director (Director prof. Dr. CFir3A ro A~AKt〕 Received Received for Publication Spt. 29. 1957

INTRODUCTION

This This report constitutes a link of a series of experimental studies on disturbance of of consciousness which have been made in our laborator y since 1944. I applied Y os 町内 method of “electronarcosis with no convul s ive phase by means of of 60 cps alternating current" (YosHII, 1953) directly to various parts of the brain of of unanesthetized cats.

MATERIALS AND METHODS

(1) (1) Unanesthetized adult cats weighing from about 2 to 3 kg. were used for experiments. experiments. (2) (2) In preliminary experiment, gradually increasing 60 cps alternating current was applied to the temporal region on both sides according 句 Yosm1's method through two steele needle electrodes which had been inserted to the level of dura passing passing through the skull at the point just above the porus acusticus externus, one electrode electrode on each side. (3) (3) Bipolar stimulating electrode .to be inserted into the brain consisted of two card clothing wires of about 0.2 mm in diameter, each of which was insulated and fixed to each other by means of Cemedine No. 240 and white lacquer except from 0.3 切 0.5 mm length of the tip. The bipolar electrode was about 0.6 mm in diameter, diameter, about 20 cm in length, and the distance between two poles was about 0.lmm.

( 4) Electrical stimulation was e百ected by means of 60 cps A. C. which w 前 supplied supplied by the apparatus made by the author (cf. Fig. 1). Stimulation voltage used used was under 10 volts, and was usually increased gradually. (5) (5) The cat was 五xed on a hammock in prone position and the four limbs were allowed to hang down naturally, therefore any movement of the limbs and the the state of muscular tension could be observed easily. After a suitable craniotomy was made in the parietal region under ether anesthesia, the CLARKE ’s sterotaxic instrument instrument (hang down type) was placed on the head of the cat. In full ＂＇叫｛ efu- lness lness fairly long after interruption of ether, the electrode was inserted into the brain brain for stimulation. 22 日本外科同函第27 巻第1 号戸川一

／ J ／乙－

Fig. Fig. 1 Electrical stimulation apparatus. Rotary SW. Position: I-A. C., 2-0FF, 3-D. C.

(6) (6) After stimulation study was over, direct current of 4.5 volts was passed through the electrode to depo sit iron. (7) (7) After physiological experiment was done, the cat was sacrificed b~· cutting both carotid arteries . The brain was fixed in 10 per cent formalin, embedded in celloidin celloidin and subjected to Nis s! stain, rnyelin stain, and iron-carmine stain. Anat- omical omical guide was obtained mainly from WINKLER and PoTTER (1914) and NIIMI (1949, (1949, 1950) and referenca was made also to JASPER (1949) and McLARDY (1951). (8) (8) Surface EEG wa s recorded with San-ei 2 channel portable electroencepha ・ lograph. lograph. (9) (9) Additional experiment was made in an attempt to s田 what change may happen in the electronarcosis induced by electrical stimulation of the mesencephalic central central gray matter, as a result of transection of the rostral end of the midbrain, cranial cranial to the stimulation point. In this experiment, the stimulation electrode had 句 be inserted into the brain before transection. The transection needed much care not to change the location of the electrode, so that an electrode w 出 devised as shown in Fig. 2, which was freely movable in accordance with possible movements

Fig, Fig, 2. The stimulation electrode specifically devised for transection experiment. a: a: The ebonite board to the fix electrode: attached to the Clarke ’s stereotaxic taxic instrument. b : The holder of the electrode. c: c: By soldering the ho lde r is connected with the electrode. After After insertion of the electrode has been done, this connection is separated by heating. The The separation of the electrode from th e holder serves to prevent movem ents of of the electrode simultaneous with transection. d : The electrode. Th e length 1.3 cm, otherwise the same ll.S the ordinary electrode. electrode. e :Fine enamelled wire. ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAI~ STE'.¥I 23 of of the brain tissue during the procedure of transection. In doing transecti on, superior superior sagittal sinus was ligated and dura was incised. Then under the guid e of of the Clarke ’ s stereotaxic instrument, the transection was executed at the rost ra l end of the mid brain by me a ns of a nkif e which was attached to the electrode holder holder of the instrument. Preliminary confirmation should have been made that the the electronarcosis could be effected by electrical stimulation of a certain locus in the the brain stem. Then transection was made, and the 泊 me locus was stimulated again .

RESULTS

(I) (I) Preliminary Preliminary experiment of electronarcosis following YosHI1's extra dural method. As the stimulation voltage increased, the cat ¥¥ T ithed and moved violentl y, but when the voltage reached about 3-4 volts, the animal became quiet, the pupils were fully dilated, and the corneal reflex as well as respon ses to painful stimuli applied applied to the auricule, to the no se tip, to the nasal septa, and to the pha1 ・ynx, disappeared. disappeared. Muscles of the limbs relaxed, and the cat did not react to heat at his his pads. The state corresponded precisely to the Yosm1's electronarcosi s. (II) (II) Electronarcosis Electronarcosis by direct stimulation of various parts of the brain. Midbrain was preferentially stimulated, but stimulation was applied also to thalamus, hypothalamus and anterior cingulate gyrus etc .. (1) (1) In 世間nces of mere insertion of the electrode on animal ’s behavior. In most c邸 es no distinct changes were induced in behavior by mere insertion of the electrode electrode into the brain except for some re st lessness, some mews, and / or anisocolia. anisocolia. However, some cats cried violently when the electrode hit certain cerebral cerebral loci, of which electrical stimulation usuall y induced more intense cn ・and more violent actions. These loci were found histologicaly to be lateral to the mesencephalic mesencephalic aqueduct. (2) (2) Classification of behaviors. During electrical stimulation, cats showed various behaviors according to var y ing loci loci stimulated, to increase in stimulation voltage, and to duration of stimulation. The behaviors were divided into following six types. 1) 1) Coma type (complete electronarcosis) Mydriasis Mydriasis （十） ; corneal reflex （一） ; pupillary reaction to light （一） ; pharyngeal yngeal reflex （一） ; auricular reflex （一） ; sneezing reflex to naso-septal stimuli stimuli (naso-septal reflex) （一） ; avoidin g reaction 句 heat at the auricle or or at the nose tip （一） ; relaxation of mu scles of the bod ~· trunk and the four four liml 万（ト） ; withdrawal reflex to painful stimuli or touch stimuli given to to any part of the body （一）;pat ell ar refl ex （ー） or （士）． 2) 2) Semicoma t~·pe (nearl y complete electronarco sis) Mydriasis Mydriasis （十） ; all or most of the above discribecl reflexes oh:o.cn 叫） le at the the head and face （一） ; relaxation of muscles of the trunk and the four 24 日本外科宝函第27 巻第1 号

limbs limbs （一） ; response to touch stimuli at a川’ limb （十）＇； that to painful stimuli stimuli at any limb （士） or （一）． The cats moved their four limbs on some occasions, but generally hung them down . 3) 3) Sham rage type All All of the reflexes at the head and face （ー） , or some of them （十） , or nearly nearly all of them （十） ; muscle ton us of the trunk and the limbs was enhanced, enhanced, and the cats writhed in screaming.

4) 4) Kinetic excitation ty ’pe. All All of the reflexes at the head and face （一） , or some of them （十） , or nearly nearly all them ( +); muscle ton us of the body trunk and the limbs was

enhanced, enhanced, or normal, and the cats moved their four limbs nearly ア continua- usly usly as. if the~ ＇ 'were struggling. In some cases, response to painful stimuli at at any limb was exaggerated. 5) 5) Convulsion t~·pe Tonic Tonic or clonic convulsions （十）． 6) 6) Type showing no behavioral change. In In some cases of this group, rn~＇ clriasis was observed. (3) (3) Classification of the experimental cases. Except Except in the group showing no behavioral changes, no consistent type of behavior behavior lasted throughout the stimulation period, and the increase in stimulation stimulation voltage usually caused behavioral change from one type to another. another. The coma type and the semicoma type were preceded by the kinetic excitation tation type in all cases except one in which coma was elicited from the beginning. beginning. In In regard to the sham rage type, some cases showed this ・ type from the beginning beginning and others showed this after the kinetic excitation type. The convulsion type was seen from the beginning in one case, in which, however, however, the kinetic excitation type followed. In In another case, the convulsion type occurred together with the sham rage type. type. Thus, Thus, all the experimental cases were classi 白ed into following 6 groups, having having respective characteristics in the reactions to stimulation. Group 1 : Cases showing the coma type without any preceding convulsion. Group 2: Cases showing the semicoma type without any preceding convulsion. Group 3: Cases showing only the sham rage type throughout or showing this this after the kinetic exciation. Group 4: Ca 日cs showing only the kinetic excitation t~·pc ・ Group 5: （冶何日ト＇ howing the convulsion t~ · pe. Group 6: （・礼団日 showing 110 behavioral change. 4) (4) Illustrating cases of each group. Group 1: ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 25

Cat 2. Female, 2.5 kg. 1st puncture on the right side of the midbrain. 5° 10' 0" Onset of electrical stimulation stimulation 5" 0.5 v. about 0.01 mA Stiffens the bod~－. 15" 15" l'dydriasis appears; urinates.

30" 1.0 v. 0.1 mA Mydriasis is present; corneal ’reflex （士）； moves the limbs lightly. 11' 11' 20" 16 v. 0.15 mA Moves the forelegs lightly; corneal reflex （士）． 12' 12' Mews mildly; corneal reflex （士） ; auricular reflex reflex （ー） ; pharyngeal reflex （士） ; reaction to to pinch at the nose tip （一）． 12' 12' 15" 2.2 Y. 0.4 mA Stops ,mewing; does not respond to heating at at the nose tip. 13' 13' 2.8 v. 0.65 mA Moves the left foreleg a little. 14 ’ 3.8 v. 1.5 mA Corneal reflex （ー） ; pharyngeal reflex （ー）； still still moving the left foreleg a little. 15 ' 4.0 v. 2.4 mA State corresponding to the coma type. 17' 17' 5.0 v. 2.6 mA The same. Cat 17. Female, 2. 7 kg. 1st puncture on the left side (midbrain) .

12 つ 5' Onset of stimulation With increase in stimulation voltage, mydriasis appears; appears; corneal reflex （士）． 15' 15' 20 " 1.0 v. about 0. 01 mA Maximal mydriasis; urinates; state corresponding nding to the coma type. 18' 18' 1.0 v. about 0.01 mA Relaxes the jaw-joint; corneal re 自ex （士）； raises raises the claws. Group 2: Cat 7. Female, 2.2 kg. 4th puncture on the right side (midbrain). 3° 3° 35' Onset of stimulation With increase in stimulation voltage, mydr ・－ iasis iasis appears; mews lightly. 1.0 1.0 v. about 0.01 mA Corneal reflex （十） ; pharyngeal reflex （十）； still still mewing. 37' 37' 1.5 v. 0.2 mA Stops mewing and becomes quiet; corneal re 自ex （ート）． 2.5 2.5 v. 0.5 mA Moves the four limbs a little excitedly; corneal eal reflex （士） ; pharyngeal reflex （土） ; auricular cular reflex （士）． 41' 41' 3.0v. 0.7 mA Still moving the four limbs; maximal mydr ・－ iasis; iasis; pupillary reaction to light （士）． 3.5 3.5 v. 1.3 mA Still moving the four limbs; corneal reflex （ー） ; auricular reflex （士）． 44' 44' 4.0 v. 1.7 mλ Still moving the four limbs ; pharyngeal reflex reflex （士） ; response to painful stimuli at the the pad (+). 26 日本外科宝函第27 巻第1 号

47' 47' 4.0 v. 2.0mA Hangs down the four limbs naturally, and doesn ’t move them; the muscle tonus is normal. normal. 50' 50' 6.5 v. 2.0mA Corneal reflex （土） ; begins to mew lightly. Group 3: Cat 24. Male, 2.1 kg. 1st puncture on the right side (midbrain). 2° 2° 50' Onset of stimulation Presently, spits, hisses and struggles. 0.5 0.5 v. about 0.01 mA Cries strongly and struggles; attacks and bites bites the pincette which is put in front of the the mouth; whirls the tail like a windmill. Moderate mydriasis; corneal retied （士）； pupillary pupillary reaction to light （十） ; pharyngeal reflex reflex （ト）； auricular reflex （ート）． 1.5 1.5 v. about 0.1 mA Crying repeatedly; raises the claws; and struggles; ggles; whirls the tail; pharyngeal reflex (±);

naso ・septal reflex （士） ; bites any objects inserted inserted in the mouth. 2.0 2.0 v. 0.2 mA Cries; corneal re 丹ex (+); raises the claws. 》 3.0 v. 0.3 mA The same as before in appearance. 58' 58' 5.0 v. 1.0 mA The same. 10.0 10.0 v. 1.1 mA The same. Group 4 Cat 22. Female, 2.7 kg. and puncture on the right side (midbraln). 1° 1° 50' Onset of stimulation Mydriasis begins. 1.5 1.5 v. 0.1 mA Corneal reflex （士） ; pharyngeal reflex （士）； auricular auricular reflex （土） ; mews when nociceptive stimuli stimuli are applied to the nose tip; moves the the four limbs excitedly; raises the claws; whirls whirls the tail. 51' 51' 2.0 v. 0.1 mA Mydriasis is present; corneal reflex （一）； auricular auricular reflex （士） ; pharyngeal reflex （士）； aぞ moves the limbs excitedly. 52' 52' 2.5 v. 0.2 mA Doesn ’t react to heat at the auricle and the nose nose tip ; nasoseptal reflex （ー）． 53' 53' 3.0 v. 0.2 mA Pupillary reflex to light （ー） ; pharyngeal reflex reflex （一） ; auricular reflex （一） , still moving the the limbs excitedly. 55' 55' 6.5 v. 1.5 mA Similar in appearance. 9.0v. 9.0v. 2.0 mA Current intensity doesn ’t increase over 2.0 mA ; similar in appearance. 58' 58' 9.0 v. 1.0 mA Corneal reflex （十） ; auricular reflex （十）； naso-septal naso-septal reflex （十） ; mews; moves the four four limbs a little, but withdraws and ELECTRONARCOSIS BY DIRECT. STIMULATION OF THE _BRAIN STEM 27

raises raises the claws when touched at the pads. Group 5 Cat 6. Female, 2.4 kg. 3rd puncture on the right side (midbrain). 10° 10° 32' Onset of stimulation Mydriasis begins. 1.0 1.0 v. 1.0 mA Generalized tonic convulsion begins; maximal myclriasis; myclriasis; pupillary reaction to light （ー）； corneal corneal reflex （一） ; pharyngeal reflex （一）； auricular auricular reflex （一） ; doesn ’t react to heat at at the auricle and the nose tip. 33' 33' 3.0 v. 2.0 mA Still convulsion is persisting; similar in appearance. appearance. 5.0 5.0 v. 2.5 mA Tonic convulsion is no more observed; moves the the four limbs excitedly; bri sk er response to stimuli stimuli at the limbs. 35' 35' 5.0 v. 2.0 mA The same. 36' 36' 30"10.0 v. 4.0 mA Current intensity doesn ’t increase over 4 mA. Similar Similar in appearance; all the reflexes examined ined at the head and face are still absent. Cat 11. Female, 2.3 kg. 2nd puncture on the right (midbrain). 12° 12° 52' Onset of stimulation 53' 53' 1.0 v. 0.5 mA Mydrias is induced; then abruptly generalized tonic tonic convulsion appears; urinates; after the convulsion convulsion is over, pupillary reaction to light is is absent; corneal reflex （一） ; auricular reflex （一） ; attacks and bites the pincette put before before the mouth; naso-septal reflex （士）； reacts 句 heat at the nose tip; horizontal nystagmus is present; brisker response to stimuli stimuli at the limbs; reacts to heat at the limbs. limbs. 1° 4' 2.2 v. 1.0 mA Generalized tonic convulsion same as before. 1° 1° 5' 3.5 v. 2.0 mA Convulsion continues for some time; after convulsion convulsion is over horizontal nystagmus is present; present; all the reflexes examined at the head and face are absent; somewhat brisker response response to stimuli at the limbs.

1° 1° 9' 3.5 v. 2.0 mA Corneal reflex （十） ; pupillar~＇ reaction to light light （一） ; auricular reflex （士） ; reacts to heat heat at the auricle (+); naso-septal reflex （十） ; a ttacks and bites the pincette put in front front of the mouth. Cat 13. Male, 3 kg. 1st puncture on the right (midbrain). 4° 40' Onset of stimulation 28 日本外科宝函第27 巻第1 号

1.0 1.0 v. 0.2 mA No change. 41' 41' 2.0v. 0.3 mA Moves the body a little. 42' 42' 3.0v. 0.5 mA Mydriasis is present; tonic convulsion of hindlegs hindlegs appears; pupillary reaction to light （十） ; corneal reflex (+ ;) pharyngeal reflex （十） ; naso-septal reflex (－十）． 46' 46' 4.0 v. 0.8mA Convulsion still continues; begins to cry strongly; strongly; attacks the pincette put in front of of the mouth; corneal reflex （十） ; naso-septal reflex reflex （十） ; auricular reflex （十） ; reacts to heat heat at the auricle. 48, 48, 5.0 v. 1.2 mA Similar in appearance. 51' 51' 6.Zv. 2.0mA Generalized tonic convulsion is extremely violent; violent; transient apnea for 30 sec; corneal reflex reflex （ー） ; pupillary reaction to light （一）； pharyngeal pharyngeal reflex （ー） ; naso ・septal reflex （ー） 52' 52' 6.2 v. 2.0 mA All reactions （十） ; attacks the pincette put in in front of the mouth. Group 6 Cat 6. Female, 2.4 kg. 2nd puncture on the left side (midbrain). 4° 24' Onset of stimulation Pupils dilate at once. 25 ’ 3.5 v. 1.5 mA Shakes the head once; corneal reflex ( + ); pharyngeal pharyngeal reflex （十）； auricular reflex （ート）； quiet; quiet; withdrawal reflex to touch at the limbs limbs （十）． 26' 26' 30"10.0 v. 5.0 mA Similar in appearance. 10.0 10.0 v. 2.0 mA Current intensity is decreased. Pupils are of normal size. Cat 29. Male 2.6 kg. 2nd puncture on the left side (anterior cingulate gyrus). 10° 10° 45' Onst of stimulation 47' 47' 4.0 v. 0.5 mA Quiet; all reflexes are positive; moves the body body trunk and the four limbs when reflexes are are examined; pupils are of normal size; at times times spontaneous movements are observed. 5.5 5.5 v. l.O mA Similar in appearance . 49' 49' 9.0v. 2.0 mA The same. 51 ’ 10.0 v. 3.0 mA The same. (5) (5) On stimulation dosage. Cases Cases showing each type of behavior have been classified according to stimulation tion dosage, voltage and intensity (cf. Table 1). C心ma tended to be induced when stimulation stimulation voltage was from 3 to 6 volts, semicoma from 1 to 5 volts, and sham rage rage and convulsion under 1 volt. And coma was apt to occur when current intensity intensity was under 3 mA, semicoma under 2 mA, and sham rage and convulsion ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 29

Table Table I.

-lv. -lv. I -2v. I -3v. ー机｜ー仇｜ー 6v. I 一7v i -8v. 一一 Coma 2 3 Semi Semi coma 2 2 3 3 Sham rage 10 I Convulsion Convulsion 8 2

ー lmA -2mA -3mA -4mA -5mA -6mA Coma 2 2 3 Semicoma Semicoma 4 5 Sham rage 12 Convulsion Convulsion 12 Incidence Incidence of each type of behavioral changes as seen with respect to stimulation voltage and and currint intensity used. Cases Cases of coma and semicoma shown in this table are only those without any preceding convulsive convulsive phase. under 1 mA. Thus it is evident that optimal dosage of stimulation, by which the coma or the semicoma type with no convulsive phase is elicited, is higher than that by which the sham rage or the convulsion type is elicited. (6) (6) Coma and semicoma seen in cases of group 1 and 2 . continued for from 3 to 4 minutes when the same stimulation voltage was kept up. (7) (7) Behavior of the animal following interruption of the electrical stimulation. In In group 1 and 2, it was noted that the cats always restored their former behavioral oral state almost simultaneously with interruption of stimulation or at the latest 30 second after that. Also in group 3, 4 and 5 they restored their former behavior as quickly as in group 1 and 2, but the animals, which showed extreme kinetic phenomena during stimulation, seemed in most cases to be exhausted after interruption tion of stimulation. In such ca~es decrease in spontaneous movement persisted for a long time, and responsiveness to various stimuli w 出 generally poor (although in some cases it was exaggerated). (8) (8) Effects on behavior of direct current passed through the electrodes. After stimulation stimulation experiments had been done, direct current with the intensity of 4.5 volts volts was transmitted for 20 seconds to loci previously stimulated in all the cases . However, this time the cats moved only slightly and no other observable behavioral change was exhibited. (9) (9) The sites of stimulation in each group. The sites of stimulation are as follows. follows. Group 1 Cat 32. The boundary between the ventromedial part of the mesencephalic central central gray matter and the reticular formation at the level of comiissura posterior. Cat 2. The boundary between the ventral part of the mesencephalic central gray matter and the reticular formation at the level of nucleus oculomotorius. Cat 17. The ventrolateral part of the mesencephalic central gray matter at 30 白木外科宝函第27 巻第1 号 the the level of nucleus oculomotorius. Cat Cat 12. Cat 25. The ventromedian part of the mesencephalic central gray matter matter near the aqueductus Sylvii at the level of nucleus trochlearis. Cat Cat 8. The ventrolateral part of the mesencephalic central gray matter caudal to to the level of commissura corporis quadrigemini postici. Cat Cat 48. Cat 49. The ventrocaudal part of massa intermedia. Group 2 Cat Cat 51. The boundary between the ventromedial part of the mesencephalic central central gray matter and the reticular formation at the level of nucleus oculomtorius. Cat Cat 39 . The ventrolateral part of the mcsencephalic central gray matter at the the level of nucleus trochlearis. Cat Cat 2. Cat 7. The boundary between the ventrolateral part of the mesencephalic phalic central gray matter and the reticular formation at the level of nucleus trochlearis. trochlearis. Cat Cat 7. Cat 14. Cat 17. The reticular formation near the ventral part of the mesencephalic mesencephalic central gray matter at the level of nucleus trochlearis. Cat Cat 33. Cat 50. The ventrocaudal part of ma 田 a intermedia. Cat Cat 46. Nucleus reuniens. Group 3 Cat Cat 24. Cat 24. The lateral part of the mesencephalic central gray matter at the the level of nucleus oculomotorius. Cat Cat 5. Cat 5. Cat 7. Cat 10. Cat 25. The lateral part of the mesencephalic central central gray matter at the level of nucleus trochlearis. Cat Cat 6. The ventrolateral margin of corpus quadrigeminum posterior. Cat Cat 12. The ventrolateral part of the mesencephalic reticular formation caudal to to the level of commissura corporis quadrigemini postici. Cat Cat 29. Cat 32. Cat 32. Cat 44. Cat 45. The medial part of the hypothalamus. Group 4 Cat Cat 18. Cat 31. Cat 35. Cat 42. The ventral end of the raphe of the mesencephalic ephalic central gray matter at the level of nucleus oculomotorius. Cat Cat 39. Cat 43. The ventromedian part of the mesencephalic central gray matter matter at the level of nucleus oculomotorius. Cat Cat 43. The boundary between the ventral part of the mesencephalic central gray matter and the reticular formation at the level of nucleus oculomotorius . Cat Cat 33. Cat 36. The reticular formation at the level of nucleus oculomotorius. Cat Cat 42. The reticular formation near the mesencephalic central gray matter at at the level of nucleus oculomotorius. Cat Cat 19. The dorsomedian part of the mesencephalic central gray matter at the the level of nucleus trochlearis. Cat Cat 13. The ventromedian part of the mesencephalic central gray matter at the the level of nucleus trochlearis. Cat Cat 16. The ventrolateral part of the metencephalic central gray matter at the the level of nucleus trochlearis. ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 31

Cat 16. C可at 25. The ventral part of the me~encephalic central gra ：＇－’ matter at the the level of nucleus trochlearis. Cat 19. Cat 20. The aqeductus S~·lvii at the level of nucleus trochlearis. Cat 18. The tc 刀 1【lai 下’ between the ventromedian part of the mesencephalic central central gray matter and the reticular formation at the level of nucleus trochlearis. Cat 22. The dorsal reticular formation near the mesencephalic central gray matter at the level of nucleus trochlearis. Cat 10. Cat 19. Cat 19. Cat 20 . Cat 20. The reticular formation at the level of of nucleus trochlearis. C3.t C3.t 6. Cat 23. The boundar~· between the caudal end of the mesencephalic central central gra~· mattEx and the reticular formation. Cat 3. Cat 4. C、at 5. Cat 5. Th reticular forIT'2.tion at the caudal end of the mid brain. Cat 20. Cat 21. Cat 21. Cat 22. The reticular formation near the mesencephalic central central gray matter at the caudal end of the mesencephalon. Group 5 Cat 1. Cat 1. Cat 7. The dorsal part of the mesencephalic central gray matter at at the level of nucleus oculomotorius. Cat 51. The reticular formation near red nucleus at the level of nucleus oculomotorius. oculomotorius. Cat 13. The dorsal part of the mesencephalic central gray matter at the level of of nucleus trochlearis. Cat 19. The ventrolateral part of the mesencephalic central gray matter at the level level of nucleus trochlearis. Cat 8. The boundar~’ between the ventral part of the mesencephalic central gray matter and the reticular formation at the level of nucleus trochlearis. Cat 6. Cat 11. The reticular formation near the ventrolateral part of the mesencephalic mesencephalic central gray matter at the leve l of nucleus trochlearis. Cat 8. The reticular formation at the caudal end of the midbrain. Cat 11 The ventrolateral part of the reticular formation at the caudal end of the the midbrain. Cat 6. The aqueductus Sylvii at the level of nucleus trochleari s. Cat 46. The corpus callosum . Group 6 Cat 6. The dorsal edge of corpus quadrigeminum posticum. Cat 29. Cat 29. Cat 34. Cat 41. Cat 43. C・at 44. Cat 45. Cat 52. The anterior cingulate cingulate g~ ’ ru只． The sits of stimulation in group 1 corresponded to the ¥ 'entral part of the mesencephalic mesencephalic central gra~・ matter, the boundan ・ between this and the reticular formati on, and the caudoventr al part of m assa intermedia. In g roup 2, sti mulated sites sites were, besides the above mentiond loci, the dorsom edial part of the mes ence phalic reticular reticular formation and nucleus reuniens (cf. Fig. 3 and 4). But it is to be noticed noticed that all the cases in which t11e-・e sites were stimulatεd did not alway s 32 日本外科宝JJ;j 第27巻第1 号

F i、. 3. Sites of stimu lation in two cases of group l 「A ) Cat 17. 1st puncture on the left si de . Th e transverse section of the the midbrain. The site of stimu lation is shown by arrow. r B 1 Cat 49. 1st puncture on the left side . The transverse sect ion of the the midbrain. Arrow indicates the site of stimu lation.

belong to group 1 or 2. But in s timulation of other parts of of the mesencephalic reticular forma - tion, tion, anterior cinglate g~·1、 us and the hJ・pothalamus etc., there was no ani- c ma! of group 1 or 2. The sites of stimulation in group 3 corresponded to the me~e ncephalic central central gT 叫 ’ matter, mesencephalic reticular reticular formation, corpus quaclrigem- inum pm:;ticum and the cauclomedial part of the h> ・pothalamus, tho~e in group 4 corresponded to the me se ncep- h alic central gra~ ’ matter, the aqueductus ctus S≫ lvii and the m ese nc e phalic reticular reticular formation, those in group 5 to to the rne sence phalic central gray

matter, the aqueductus S ：：，・ lvii, mesencephalic ephalic reticular formation, and the corpu s callosum, and those in group 6 to to corpus quadri gem inum po st icum and Fig ・. 4. Sketches showin g the site s of stimulation in in the cases of 広roup I and 2. the ant 巴rior cin gu l ate g~Tuぉ． A-D: Tran sve r se sect ion s of the mi rlbr ai n. Some remarks will be made in the E: Trans verse se ction of the clienc 巴phalon. 9 : Coma. A ・ Semicoma. following about the relations of ¥' arious ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 33

Table Table 2. Location Location of the electrical stimulation stimulation Group I N白山 I Farb … ｜T… m 1 4 2 Central Central gray matter 3 7 28 4 11 5 5 ,,

1 2 Boundar;11 Boundar;11 between the ventral /f h! 2 3 of of the central gray matter an 3 。 10 reticular reticular formation 4 4 69 69 5 。 2 3 Reticular Reticular =formatio n 3 1 26 4 17 5 5

3 1 Posterior Posterior colliculus 2 4

4 2 Aqueductus Aqueductus 3 5 Incidennce Incidennce of each type of reactions as seen in stimulation of various mEsencephalic structures. structures. ' mesencephalic mesencephalic sites to the types of reaction on stimulation (cf. Table 2). In In stimulation of the mesencephalic central gray matter, various types of reaction reaction were seen, the an imal s belo・gning to group 1, 2, 3, 4 and 5. Coma and semicoma in group 1 and 2 were elicited by stimulation of the ventral part of it, sham rage in group 3 was elicited by stimulation of the lateral part, kinetic excitation excitation in group 4 I乃v stim ulation of the midlin e and in the ventral region, and convulsion convulsion in group 5 b~・ that of the dorsal part. In stimulating the mesencephalic central central gra? matter at the lev el caudal to commissura corporis quadrigemini postici, various various responses could be elicit ed from one and the 回 me area. Incidence Incidence of elicitation of coma by stimulation of the ventral part of the mesencephalic mesencephalic central gray matter was about 22 )< ;, and that of elicitation of coma and semicoma was about 37 ヲ. In 9 out of these cas 田 the ventromedian part of the the central gray was stimulated with resulting kinetic excitation in 7 and coma and semicoma only in 2. Thus stimulation of the ventral part of the central gray excluding excluding the median portion induced coma in 22 % and coma and semicoma in 44% of the cases. (10) (10) Comparison was made between the effect of the gradual stimulation of increasing increasing intensit y and that of the sudden stimulation of consistent intensity (cf. 34 34 日本外科宝函第27 巻第1号

Table Table 3. Group Group No. ef cat Conditions Result (grouping) 8 I 4v. 2mA (6v . 4mA) I7 I7 I Iv. about O.OimA (Iv. about O.OimA) 25 25 I 4v. 2mA (4v. 2mA) 32 32 I 6v. ImA (6.5v. 2.5mA) 48 48 I 3.4v. ImA (5.5v. 2mA) 49 49 I 2.7v. ImA (2.7v. ImA)

う qaco ？－内， daaτE1u 4v. 2mA (4v. 2mA) 2 zv. 0.5mA (2v. 0.25mA) uRU －－ 1.8v. 1.8v. 0.5mA (3¥'. ImA) In In each case coma or semicoma was elicited at first by gradually increasing stimulation. Parameters Parameters of stimulation at the time when coma or semicoma was induced are shown in parenthesis. parenthesis. When the animal regained full responsiveness, abrupt stimulation of constant intensity intensity was made to the same loci using parameters shown without parenthesis.

Table 3). Of 9cases in which coma or semicoma was induced by the gradually increasing stimulation, stimulation, the same type of response was induced by the sudden stimulation in 8 cases. Thus, it was found that the coma or semicoma with no convulsive phase (in group 1 and 2) could be elicited not only by the gradually increasing stimulation, but also by the sudden stimulation. The same was true of groups 3, 5 and 6, but many cases of group 4 showed the preceding convulsive phase when the sudden stimulation was made. (11) (11) Square pul 日es were used for stimulation in some cases instead of alternating current, and the same results were obtained when square pulses were of 60 per second (cf. Table 4).

Table Table 4.

No. No. of cat Group Conditions j Result （邑： rou 向）

－－噌唱ヴ，弓 A 4v. lmsec τi 勾んの itnudnu 3.2v. lmsec 勾Jun JRU内 6q 15v. 15v. 0.2msec u， ’ の u lOv. lmsec ur Conditions Conditions of square pulse stimuli applied to the sites where gradually increasing stimulation induced induced coma or semicoma.

(12) (12) Electroencephalographic findings. Surface EEGs were recorded in some cases of group 2 (semicoma) during stimulation stimulation by square pulses (cf. Fig. 5). As seen in the figure, no eminent slow wave appeared, but after-discharge-like-wave was observed during semicoma. (III) (III) From the above results, it became clear that coma and semicoma could be ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STE:¥I 35

60~ ， IS 眠 OJ ・銅色

且川明州制）i ..~λ

ー」，..，＿＿（ IO•fV.

』t

Fig-. Fig-. 5. Strips 1 and 2: cat 39. Square pulse stimulation ( 60 per se :: ., 15 vol ts, 0.2 ms ec ) of of the mesencephalic central gray matter. Sernicoma was indusced. Strips Strips 3-6: cat 50. Square pulse stimulation ( 60 per sec ., IO volts, I rnsec ) o:f rnassa inter inter media. Semicorna Semicorna was induced. Tim e in parenthesis ind icate period of par tial abridgment of of the record.

produced produced in some cases b~’ alternating current current stimulation of the mesencephalic central central gray matter. Thus, an attempt was made to transect the rostral part of of the midbrain, supposing that this procedure procedure might exert some foundame- ntal ntal influence on the stimulation effect. (1) (1) Partial transection. In some cases of groups 1, 2, 3, 4 and 5, 5, where electrical stimulation was given to to the me i': encephalic central gray matter, ter, partial transection covering the Fig-. Fig-. 6. Transverse section of the midbrain mesencephalic central gra y matter (cf. at at the level of nucleus oculornotorius, Fig. 6) was done cranial to the stimu- howing howing the extent of the lesion effected effected bv the partial transection lation point. Electrical stimulation was in in cat 68 . then made again, but there wes almo st no change in the e汀ect of stimulation as compared with that before tran section. (2) (2) Total transection. Total Total transection of the midbrain (cf. Fig . 7) was clone in some cas 田 of groups groups 1 and 2. After the transection the cat became quiet, but all nociceptive reflexes were preserved; preserved; the animal screamed b~ · the electrical stimulation of the sciatic nerve. In In partial or total transection, when it was done rapidl~＇， the cat suddenly fell 36 日本外科宝函第27 巻第l 号

Fig. Fig. 7. into coma for some moments. Cat 68. male, 3 kg. Partial Partial tran secti on of the brain stem was made rapidly at the level of of oculomotor nucleus as shown in Fig. Fig. 6. Instant!>・ the cat showed tonic tonic stretching of the four limbs for for some moments and the state corresponding corresponding to coma or semicorrr. ensued ensued for 15 minu~es, and finally normal responsiveness was restored. After the mesencephalic tran - (A ) Transverse section of the rostral ;;art of the section had been done, electrical midbrain midbrain showing the extent of the lesion stimulation was carried out through effected effected by the total transection. the electrodes previously inserted and fixed in a locu s in the central gray where a stimulation study had been been done before the transection. Coma or semicoma was induced b:: b:: the stimulation in the same waY as as before transection, and the cat did did not cry, unless high voltage square square pulses were used for stimulation lation of the sciatic nerve . Cat 85. Female , 26 kg. 1st puncture puncture on the left side of the midbrain. midbrain. (B ) Mitlsa gitta l reconstruction of the brain stem. The site of electrical stimulati- Th e plan 巴 of transection is shown . on: on: the mesencephalic central gray matter at the level of nucleus trochlearis. Coma was elicited b＞’ the electrical stimulation with the intensity of about 2 volts volts and 0.2 mA. As soon as the stimulation ceased, the cat mewed lightly, and nociceptive nociceptive refl exes reappeared. Then, total transect ion was done at the rostral end of of the midbrain. After 30 minutes, all nociceptive reflexes returned, and the cat screamed when square pul se st imulation was a百orded to the sciatic nerve with the

intensity intensity of 10 volt 日， the frequency of 60 per second and the pulse duration of 1 msec. msec. The cat fell into coma when the second electrical stimulation of the central gray was made with the intensit y of 3.5 volts and 0.4 mA. During coma, the cat cat screamed when strong square pulse stimulation was afforded to the sciatic nerve with with the int ensit y as hi gh as 35 volts but with the sa me fr eque nc y and pulse

duration duration a日 in the previous te ぉt.

The site of tram 古ection confirmed at autopsy: the frontal plane passing through the the ro ぉtal end of corpus quadrigeminum anticum an d the exit point of n. oclomoto - ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 37

rius rius from the brain stem (cf. Fig. 7). Cat 88. Female, 2.5 kg. 1st puncture on the left side of the midbrain. The verified site of electrical stimulation: the mesencephalic central gray matter at at the level of nucleus trochlearis. Semicoma was elicited by electrical stimulation of about 4 volts and 0.4 mA. After After the transection, the cat screamed when stimulation was made to the sciatic nerve nerve with square pulses of from 0.2 to 0.4 volts, 60 per second and 1 msec in pulse pulse duration. The response of the sham rage type was elicited by the second electrical electrical stimulation with 60 p. s. AC of 0.5 volts and about 0.01 mA. Then the electrodes electrodes were inserted more deeply by about 0.2 cm. At this time, the cat fell into into semicoma when electrical stimulation of 1.5 volts and about 0.01 mA was effected. effected. During semicoma the cat mewed faintly when stimulation was made to the the sciatic nerve with square pulses of 30 volts. The verified site of transection: Same as in case 85. In In cases 85 and 88 the complete electronarcosis was induced by extraduaral the electrical electrical stimulation before as well as after mesencephalic transection. From the above results, is it apparent that coma or semicoma can be elicited both both by the extradural electrical stimulation and by the directly applied electrical stimulation stimulation of the mesencephalic central gray matter, even which total transection had been made at the rostral end of the midbrain.

DISCUSSION

The electronarcosis w 部 induced, though not regularly, by stimulation of certain parts parts of the brain the stem; caudoventral part of massa intermedia, the ventral part part of the mesencephalic central gray matter, the boundary between the central gray and the reticular formation, and the dorsal reticular formation near the central central gray matter. The narcosis evoked from the last mentioned locus ・was not so so deep as 出 at from the other parts. Thus is it likely the that electronarcosis is more closely related to massa intermedia and the ventral mesencephalic central gray matter than to the mesencephalic reticular formation. The state of electronarcosis grossly corresponds to coma or semicoma, and is characterized characterized by loss of all nociceptive reflexes, reduction in muscle tone, and lack in in voluntary and involuntary movements of the body trunk and the four limbs. But, But, is it to be noticed that coma or semi-coma was regularly induced ・by the extradual extradual electrical stimulation, whereas it was less frequently induced by the electrical electrical stimulation of the midbrain. In In the sham rage or the kinetic excitation type, the animal screamed and/ or writhed writhed (without any concomitant convulsive movements of the body), but showed only only partial impairment nociceptive refleces. These states are not unlike to the excitement excitement stage of general anesthesia in which consciousness seems to be impaired to to a degree. certain The two types were induced by stimulation of the mesencephalic halic central gray matter or a part of the mesencephalic reticular formation, cloE"ely neighboring neighboring the central gray matter. These areas included are in the regions from 38 日本外科宝函第27 巻第1 号 which coma could be induced. On the other hand, there were man y cases in which sham rage and kinetic excitation were elicited by stimulation of the reticular formation ation fairly apart from the m 回 encephalic central gray matter. It It should be noted that the extradural electrical stimulation did not effect the~e types types of reaction, but only coma and semicoma. The reason may be in that the extradural extradural stimulation may widel y excite a large part of the midbrain. This assumption assumption is based on the fact ob s erved by lKusHIMA that coma w as produced by the the chemical stimulation with a large amount of diluted sublimate solution injected in in a wide extent of the mesencephalic reticular formation, whereas the stimulation (chemical (chemical or electrical) of a 1:mall extent of this structure predominantly induced exCitement exCitement of the reticular activating system accompanied by behavioral arousal as

陀 ported by Magoun. In In our midbrain-animal it was confirmed that all reactions were nearly the same as before transection; nociceptive reflexes were preserved, sham rage or kinetic excitation excitation could be caused by stimulation of the midbrain caudal to the transection, and stimulation of the mesencephalic central gray matter could elicit behavioral changes changes of the type of coma or semicoma. Therefore Therefore it seems that our experimental coma induced by mesencephalic stimulation stimulation has nothing to do with the cerebral cortex and with the di 百use thala- mocortical mocortical projecting system of Morison and Dempse y, as well as with the ascending reticular reticular activating sy stem of Magoun. It rather seems that the portion of the brain brain stem ex tending from ma s sa intermedi a to the ventr al mesencephalic central gray matter relates closely to the electronarcosis or the coma (unresponsiveness to nociceptive nociceptive stimuli) reported here. In summarizing, the electronarcosis, or coma as well as semicoma seen in groups groups 1 and 2 of our experiments, is effected by neural mechanisms of the midbrain midbrain and nervous structures caudal to it. Especially the ventral area of the mesenceph alic central gra y matter seems to play the most important part in these mechanisms, mechanisms, in which the mesencephalic reticular formation etc. more o士less participate participate too. However it is possible that coma is caused more easily by stimulating stimulating the whole extent of the midbrain, than a certain circumscribed locus in in the midbrain.

CONCLUSION

The disturbance of consciousness dealt with in this paper is that of the consciousness consciousness of lower level (i. e. of reflex nature), and can be e古田ted by the alternating alternating current stimulation of the ventral part of the mesencephalic central gray matter. As to the disturbance of consciousness of higher level nothing can be discussed discussed from the results of our experiments. Our conclusion is th at th e ventral m ese nc ephalic central gr ay matter plays an important important role in the disturbance of lower consciousness. ELECTRONARCOSIS BY DIRECT STIMULATION OF THE BRAIN STEM 39

Refere!lces Refere!lces study of thalamo-cortical relations. Am . J. 1) 1) Araki, C., T. Taketomo and T. Toda: Coma Physiol., 135, 281-292, 19 .42. 18) Moriyasu, H.: puncture. puncture. Acta Scholae Med. Univers . Kioto Unconsciousness evoked by stimulation of Jap., Jap., 27, 205-211, 1949 . 2) Akert, K. , W. P. lower stem.brain Presented at the 53rd Koella Koella and R. H€ss, Jr., Sleep produced by Congress of Japan Psychoneurological Socie- electrical electrical stimulation of the thalamus . Am. J. ty, Tokyo. 1956 . 19) Nagai, T.: Cerebral Physiol., Physiol., 168, 260-267, 1952 3〕French, J. D., blood flow dur 泊 g coma induced by the F. F. K. Ven Amerongen and H. 明T. Magoun: An stimulation of the periaqueductal gray ma- activating activating system in brain stem of monkey, tter (coma puncture ). Acta Scholae Med. A. M. A. Arch. Neurol. Psychat., 68, 577 -590 Univers. Kioto Jap ., 31, 193-214, 1954 . 1952. 1952. 4) Gerard, R. W ., W. H. Marchall and 20 ) Niimi, K.: ComparatiYe anatomical study L. L. J. Saul: Electlical activity of the cat ’s of the thalamus of mammals, Brain ’ Reserches, brain. brain. Arch. Neurol. Psychiat., 36, 675 , 1936. 7, 88-99, 1950. 21) Niimi, K.: Ziir vergleich- 5) Girndt, 0.: Die Ermitteliing der Wirkii- enden Cytoarchitektonik der vorderen, medi- ngsst むke von Schlafmitteln mit Hilfe der anen iind medialen Kerngriippe des Sehhiigels Korperstell-und Korperstell-und Labyrinthrefiexe . I. Arch. f. des Meschen. Acta Scholae Med. Univers . exp. exp. pathol. ii. Pharmakol., 164, 118-157. 1932. Kioto Jap ., 'l!l, 116 ・132, 1949 . 22) Sakata, K.: 6) 6) Hanbery, J., C. Ajmone-Marsan and l¥1. Electroencephalographic studies on coma in- Dilworth : Pathways of nonsp ec ific thalamo- duced by stimulation of 、arious parts of the cortical cortical projection system. EEG. Clin. Neur- brain in mt. Bein g prepared for publication. ophysiol., ophysiol., 6, 103-118, 1954 . 7) Hrns, W. R.,: 23) Schiller, F.: Consciousness reconsidered. The diencephalic sleep centre. Brain mcch- Arch. Neurol. Psychiat., Chicago 67, 199, 1952. anisms and consciousness. A sym posium 24 ）羽Tinkler, C. and A. Potter: An anotomic- organized organized by the council for international al guide to experimental researches on the organization organization of medical science. !954. cal ’s brain .、'fi'. Versluys, Amsterdam. 1914 8) 8) Ikushima, H., 1955: Uncousciousness by 25) Y abuno, S.: Co rna puncture by means of injection injection of dilute solution of cor r osive subl- nicotinization. Acta Scholae med. ’Uni vers . imate. imate. Presented at the 52nd Congress of Kioto Jap, 32, 32-51, 1954. 26) Yoshii, N., : Japan Psychoner.rological Society, Kioto. Physiological researches of Eilepsy, No-to- 9) 9) Ishii, S.: Coma puncture (monograph ), shinkei, 5, 57, 1953. Kioto. Kioto. 1944. 10) Jasper, H .: Diffuse projection Abbr0viations Abbr0viations in Figures systems: systems: the integrati¥"e r.ction of the thalamic ABC reticular reticular system. EEG Clin. Neurophysiol. , I, ph Aqueduct 40 5-42 0, 1949. 11 ) Ja sper, H ., C. Ajmone- Basis pedunculi Marsan and J. Stoll: Coriticofu g al proj 巴ctions C hiasma neni optici to to the stem.brain A. l¥I. A. Arch. Neurol. C. I Capsula int er na Psych iat., 67, 155-171, 1952. 12 l l¥''og-o u n, H. C.Q.a Corpus quadrigeminum anticum W.: An ascending reticular acti¥"ating s :vstem C.Q.P C orpus quadrigeminum posticum in in the brain stem. Arch. Neurol. Psychiat., C.C.Q .P Commiss・ura corporis quadrigemi- Chicago, Chicago, 67, 145, 1952. 13) Magoun , H. W. ni postici 1950: 1950: Caudal and cephalic influence of the C.P Commissura posterior brain brain stem reticular formation. Phy siol. Rev., F.R Formatio reticularis 30, 30, 459 ・47 4, 1950 . 1 4) Matsuna ga , M.: Exp eri- G. g. l Ganglion geniculatum laterale mental studies on coma induced by stimulat- Inf Infundibulum ion ion of Yarious parts of the brain in cat. Be- :'II. i Massa intermedia ing ing preparted for publication. 15 ) Matsunaga N. III :Nucleus oculomotorius M, K. Sakata, H. Ikushima and S. A sai: Coma N.IV Nucleus trochlearis induced induced by chemical and electrical stimulation N e. III ド1. oculomotorius of of brain stem. Presented at the 13 th Corig- p Pons ・ ress ress of Japan Neurosurgi ca l Soci e ty, Tokyo. P.P .c Pes pedunculi cerebri 1954. 1954. 16) Mc Lardy, T., 1951: Diffuse thala- R.m Nucleus reuniens medianus mic projection to cotex. An anatomical crit- S. gr.c Substantia grisea centralis ique. ique. EEG Clin. Neurophsiol., 3, 181-188. Tr.op Tractus opticus 17) 17) Morison, R. S. and E 羽T. Dempsey: A V.III Ventriculus III 40 40 日本外科室函第27 巻第1 号

V.IV Ventriculus IV V.dA Fasciculus Vicq d’Azyr

和文抄録脳幹部を直接刺戟する電気麻酔実験

京都大学医学部外科第 l 講座（荒木千里教授指導）浅井茂

私達は吉井氏の無痘壁電気麻酔を無扇面キ猫のi脳の冬特にその概構に重要な部位を占めるが，中脳網様織等

所に直接適用する実験を行いp 叉中脳吻側ょ； 1：に1黄’九公も関係している．供し之等個々の部分が刺戟される場切断を加えた猪で，同様の電三~＊リ戦実験を中 Jli/i に／j2 て合よりも，会体として中脳が広く刺戟された場合に電

行いp 検計を加えた．その結果よりして，電気麻酔状気麻酔状態が起り易いもの h 様に思われる．態は中脳以下の機構によるもので，中脳中心灰白寅が